Comparative Cardiovascular Safety of Dementia Medications: A Cross-National Study
Article first published online: 23 NOV 2012
© 2012, Copyright the Authors Journal compilation © 2012, The American Geriatrics Society
Journal of the American Geriatrics Society
Volume 60, Issue 12, pages 2283–2289, December 2012
How to Cite
J Am Geriatr Soc 2012.
- Issue published online: 11 DEC 2012
- Article first published online: 23 NOV 2012
- American Heart Association Pharmaceutical Roundtable
- BMS/Sanofi, Eli Lilly, and Johnson & Johnson
- Midcareer Development Award. Grant Number: K02HS017731
- Agency for Healthcare Research and Quality
- U.S. Department of Health and Human Services
- cardiovascular system;
- cholinesterase inhibitors;
- drug toxicity;
- United States
To compare the cardiovascular safety of currently marketed dementia medications in new users in the United States and Denmark.
Retrospective cohort study.
Nationally representative sample of Medicare beneficiaries from 2006 through 2009 and nationwide Danish administrative registries from 1997 through 2007.
Individuals treated with a dementia medication aged 65 and older.
Hospitalizations for myocardial infarction (MI), heart failure, and syncope or atrioventricular block in both cohorts; fatal or nonfatal MI and cardiac death in the Danish cohort; and all-cause mortality in sensitivity analyses.
In 46,737 Medicare beneficiaries and 29,496 Danish participants, donepezil was the most frequently used medication. There were no substantial differences in the risk of MI or heart failure between participants using donepezil and those using other cholinesterase inhibitors (all hazard ratios (HR) crossing 1). In the Danish cohort, memantine was associated with fatal or nonfatal MI (HR = 1.33, 95% confidence interval (CI) = 1.08–1.63), cardiac death (HR = 1.31, 95% CI = 1.12–1.53), and a trend toward higher rates of hospitalization for MI (HR = 1.31, 95% CI = 0.98–1.76). Memantine was also associated with greater risk of all-cause mortality in the Medicare (HR = 1.20, 95% CI = 1.13–1.28) and Danish (HR = 1.83, 95% CI = 1.73–1.94) cohorts, suggesting that sicker individuals were selected for memantine therapy.
Cholinesterase inhibitors have similar cardiovascular risk profiles. Associations between memantine and fatal outcomes in Denmark may be related, in part, to selection of sicker individuals for memantine therapy.